The present invention relates to a process for non-invasive, non-ionizing diagnostic and treatment applications for cancers such as breast cancer and more generally for any body cells or biological species that can be targeted by an appropriate binding moiety. More particularly, the present invention relates to non-invasive, non-ionizing diagnostic applications involving the delivery of magnetic markers and the in vivo manipulation of the magnetic domains of such magnetic markers. The present invention further relates to a process for the non-invasive measurement of temperature of tissue through the measurement of Barkhausen noise associated with magnetic domains delivered to such tissue. The present invention is the result of a contract with the Department of Energy (Contract No. W-7405-ENG-36).
Breast cancer is a serious national problem that will affect approximately twelve percent of women in their lifetimes. Breast cancer is presently the second leading cause of death in women in the U.S. and is one of the most publicly visible and diagnostically investigated diseases. Although probably the most common diagnostic used, physical (both self- or physician administered) examinations are generally a poor diagnostic method as only well developed tumors will be detected. Even palpable changes in breast tissue are poor indicators of the existence of a tumor with an accuracy rate of only between about 60 and 85 percent. Malignant palpable tumors are also typically well developed and thus have poor prognostic outcomes compared with tumors that have been identified early, before they become palpable. For these reasons, mammography or other diagnostic techniques that enable earlier detection of breast cancer are essential to increase both the diagnostic reliability and prognostic outcome.
Mammography is the most common method used to screen women over 40 and younger women in a high-risk group for early detection. Mammography is one of the most powerful and widely used tools for early diagnosis of breast cancer. It has limitations, however, such as for women who have mammographically positive breast tissue resulting from scar tissue from previous radiation therapy, injury or surgery. Mammographically distinguishing between benign and malignant abnormalities is also difficult. Due to the various limitations of the present diagnostic techniques, work has continued on improved diagnostic systems.
Alternatives to mammography (as well as other forms of cancer) are currently being explored including magnetic resonance imaging (MRI), positron emission tomography (PET), and scintimammography. MRI has shown potential for detection of breast cancer, however it remains an experimental tool that typically requires using contrast agents and there exists no standardization at this date. F18-(2)-FDG is widely used in PET studies and shows evidence from in vitro studies that it may accumulate in breast cancer cells. The most significant impediments to PET are the extremely high cost of the instrumentation and associated cyclotron, the limited availability of these machines, and the collateral radiation dose associated with this technique. Scintimammography is becoming a principal alternative to mammography where additional confirmation is needed, or mammography simply is not yielding satisfactory results. The method is achieving considerable success but is largely limited by the significant collateral radiation dose to other organs.
Once malignant tumors are positively identified, the most common treatment is surgical removal of the tumor and any associated lymph nodes through one of a number of forms of breast conserving therapy or mastectomy plus sentinal or general lymph node dissection. These methods result in various degrees of disfigurement, morbidity, and emotional distress. Subsequent to surgery, radiation and/or chemotherapy are used to attempt to eradicate tumor cells that may have migrated from the original cancer site.
Various adjunctive therapies have been proposed and tested including hyperthermia. The literature most commonly refers to hyperthermia as an adjunctive therapy to radiation or chemotherapy. Various methods including microwave radiation and heating of magnetic implants have been used to induce the hyperthermia. The belief is that increasing tissue temperature a few degrees (Celsius) increases metabolism and renders tumor cells more susceptible to radiation and/or chemotherapy. This belief has not been conclusively proven. Microwave radiation has also been used to deposit sufficient energy to cause necrosis of tumor cells (e.g. kill the tumor cells) using phasing techniques that focus the energy. This technique, however, causes significant collateral damage in healthy tissue because of substantial energy deposition outside the tumor itself.
Klaveness et al. (U.S. Pat. No. 5,735,279) have described use of SQUIDS for magnetometric imaging of a body using ferromagnetic, ferrimagnetic or paramagnetic materials. Gordon (U.S. Pat. Nos. 4,106,488 and 4,735,796) has described treatment of cancer by use of minute particles possessing ferromagnetic, paramagnetic or diamagnetic properties together with application of a high-frequency alternating electromagnetic field to inductively heat intracellular particles. Despite these efforts, a further search for alternative treatments to surgery remains.
An object of the present invention is a diagnostic and treatment technique for a cancer such as breast cancer wherein a magnetic material attached to a delivery agent is administered to a subject in a manner adapted for localization of a sufficient amount of said magnetic material to a location having cancerous cells, followed by inducement of localized heating of said cancerous cells via manipulation of magnetic domains within said administered magnetic material.
Still another object of the present invention is the use of a intracellular viscous heating process to attain the desired localized heating.
Another object of the present invention is a technique for measuring cellular temperature using measurement of Barkhausen noise.
Still another object of the present invention is the use of the cellular temperature via the measurement of Barkhausen noise for a feedback loop in the treatment technique.